AU728928B2 - Anticancer drug - Google Patents

Anticancer drug Download PDF

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Publication number
AU728928B2
AU728928B2 AU87021/98A AU8702198A AU728928B2 AU 728928 B2 AU728928 B2 AU 728928B2 AU 87021/98 A AU87021/98 A AU 87021/98A AU 8702198 A AU8702198 A AU 8702198A AU 728928 B2 AU728928 B2 AU 728928B2
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Australia
Prior art keywords
cancer
bamboo
powder
composition according
pharmaceutical composition
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Ceased
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AU87021/98A
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AU8702198A (en
Inventor
Shigetomi Kumon
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Asahi Corp
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Asahi Corp
Asahi Tsusho Co Ltd
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Publication of AU8702198A publication Critical patent/AU8702198A/en
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Publication of AU728928B2 publication Critical patent/AU728928B2/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/896Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • A61K36/8962Allium, e.g. garden onion, leek, garlic or chives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/42Cucurbitaceae (Cucumber family)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/61Myrtaceae (Myrtle family), e.g. teatree or eucalyptus
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/899Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/10Preparation or pretreatment of starting material
    • A61K2236/15Preparation or pretreatment of starting material involving mechanical treatment, e.g. chopping up, cutting or grinding

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  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Biotechnology (AREA)
  • Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Epidemiology (AREA)
  • Medical Informatics (AREA)
  • Botany (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Mycology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)

Description

1
AUSTRALIA
PATENTS ACT 1990 COMPLETE SPECIFICATION FOR A STANDARD PATENT
ORIGINAL
Name of Applicant/s: Actual Inventor/s: Address of Service: Invention Title: Asahi Corporation Shigetomi KUMON BALDWIN SHELSTON WATERS MARGARET STREET SYDNEY NSW 2000 "ANTICANCER DRUG" The following statement is a full description of this invention, including the best method of performing it known to us:- (File: 21329.00) la ANTICANCER DRUG BACKGROUND OF THE INVENTION The present invention relates to an anticancer drug effective in preventing colon and rectum cancer (cancer of the large intestine) of a high incidence, reducing the cholesterol value in plasma, and lowering the blood-sugar levels of diabetics.
Cancer has been taking a heavy toll of lives every year, and has recently become a representative of fatal diseases. On the other hand, research and development in medicines for, and S""treatments of, cancer are progressing rapidly. However, no fully *e e effective medicine has been developed, and no fully effective treatment has been established. Accordingly, the prevention of cancer is most important.
*One of the cancer-preventing measures is to remove such factors in our living environment as may cause cancer. Among such factors, food is the most fundamental factor. Food additives may contain cancer-inducing agents. Carcinogens may be produced S 20 while food is stored or cooked. It is known that the quality of food and nutrition have considerable relevance to the canceration.
For instance, vitamin A contained in vegetables is supposed to be effective for cancer prevention, and Vitamin C lowers the level of the production of nitrosamine in our bodies.
Vegetable fiber improves bowel motions and reduces the incidence of colon and rectum cancer.(P.894, Vol. 3, Heibonsha's Encyclopedia) It is important, therefore, to avoid foods which may be cancer-causing factors or contain carcinogens and to have foods which contain large quantities of vitamins and vegetable fiber.
As mentioned above, no fullyeffectivemedicine for cancer -2is available, and canceration processes have not completely been elucidated yet.
Accordingly, it has not yet been elucidated which, in concrete terms, of such foods as containing large quantities of vitamins and fiber can prevent cancer effectively.
On the other hand, even if there is available a drug which prevents cancer quite effectively, it would tend to have side effects due to its very nature that it acts strongly on human bodies.
It is an object of the present invention to overcome or ameliorate at least one of the disadvantages of the prior art, or to provide a useful alternative.
SUMMARY OF THE INVENTION According to a first aspect the invention provides a pharmaceutical composition suitable for use as an anticancer drug and comprising bamboo powder derived from a lower no branch culm portion of a three-year-old or older bamboo.
According to a second aspect the invention provides a method of producing a pharmaceutical composition suitable for use as an anticancer drug, the method 15 comprising: providing as a starting material a lower no branch culm portion of a threeoooyear-old or older bamboo.
According to a third aspect the invention provides a method of reducing the incidence of colon or rectal cancer in a subject, the method comprising orally administering to the subject a pharmaceutical composition according to the first aspect.
According to a fourth aspect the invention provides a method of treating cancer including the step of administering to a patient in need thereof a composition according to the first aspect.
According to a fifth aspect the invention provides the use of a composition according to the first aspect for the manufacture of a medicament for the treatment of cancer.
BRIEF DESCRIPTION OF THE DRAWING The features and advantages of the present invention will become more clearly appreciated from the following description in conjunction with the accompanying drawing, in which: Fig. 1 is a flow sheet showing the process of one embodiment of anticancer drug of ;0 the present invention.
21329-00.DOC -3- DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS With reference to the drawing, a preferred embodiment of the present invention will now be described.
In Fig. 1, the letter A represents an anticancer drug embodying the present invention. The ingredients of the anticancer drug A consists of a main ingredient of bamboos IS and accessory ingredients. First, the main ingredient of bamboos 1S will be described. Any kinds of bamboos can be used as bamboos IS, for any kinds of bamboos contain fiber, lignin, etc. For example, black bamboo (Phyllostachys nigra), common Japanese bamboo (Phyllostachys bambusoides), mosochiku (a species of ooo** e o**o e 21329-00.DOC 4 thick-stemmed bamboo, or Phyllostachyspubescens), and soon can be used as bamboos IS.
Any portions of a bamboo can be used as bamboos IS, the main ingredient of the anticancer drug A. In particular, the lower no-branch culm portion of a three-year-old or older bamboo is suitable, for this portion contains more fiber, lignin, etc. than the other portion. Although we usually don't eat this portion of a bamboo, the inventor of the present invention dared to use this portion as the main ingredient. The effect of doing so will S. 10 be described later.
**.Bamboos cut down in any seasons can be used as bamboos IS, the main ingredient of the anticancer drug A. In particular, bamboos cut down during the period of three months before the season of bamboo shoots are most suitable as bamboos 1S, for 15 bamboos accumulate nourishment in the period so that they can nourish bamboo shoots in their season. Therefore, bamboos cut down in the period contain more fiber, lignin, etc. than those cut down in the other periodinayear. Its effect will be described later.
20 Bamboos iS are reduced by a grinder to fine powder 1 o.
of 0.1-20 micrometers or so.
The accessory ingredients of the anticancer drug A comprise the following materials.
Pumpkin seeds 2S are seeds taken from mature pumpkins and dried. These pumpkin seeds 2S are reduced by a grinder to fine powder 2 of 0.1-20 micrometers or so.
Dried cloves of garlic 3S are reduced by a grinder to fine powder 3 of 0.1-20 micrometers or so.
Powdered cheese 4 can be of any cheese without particular limitation.
Wheat flour 5 is to form the anticancer drug A into a granular, or bar-like, or some other shape, and any wheat flour 5 without particular limitation can be used as wheat flour 5. Powder of glutinous rice may be used instead of wheat flour Any water without particular limitation can be used as water 6.
Moreover, all the accessory ingredients of pumpkin seed powder 2, garlic powder 3, powdered cheese 4, wheat flour and water 6 can be dispensed with. However, as bamboo powder 1 alone is not suitable for taking it by mouth, it is preferable to add such accessory ingredients to the main one and mix them.
10 A process for preparing the anticancer drug A will now be described in sequence.
First, bamboo powder 1, pumpkin seed powder 2, garlic powder 3, powdered cheese 4, wheat flour 5, and water 6 are mixed *in a mixing ratio described later (10P) The mixture is steamed for about two hours and allowed to mature for 48 hours at normal temperature (20P). Then, the compound is formed into a desired shape such as a granular, or bar-like, or any other shape Air of normal temperature is blown into the shaped pieces to dry them (40P), and they are further allowed to mature for 48 hours (50P) to become anticancer drug A of this embodiment.
The mixing weight ratio of the main ingredient of bamboo powder 1 and the accessory ingredients of pumpkin seed powder 2, garlic powder 3, powdered cheese 4, wheat flour 5, and water 6 will now be described.
Table 1 shows a mixing weight ratio of the main ingredient of bamboo powder 1 and the accessory ingredients of pumpkin seed powder 2, garlic powder 3, powdered cheese 4, wheat flour 5, and water 6. The higher the mixing weight ratio of the main ingredient of bamboo powder 1, the higher the medicinal effect of the anticancer drug A.
Table 1 Mixing Weight Ratio 6 Bamboo powder 1: Pumpkin seed powder 2: Garlic powder 3 Powdered cheese 4 Wheat flour 5 Water 6: Appropriate quantity To make it easy for us to take the anticancer drug A of this embodiment bymouth, itmaybe formed into tablets, grains, 10 bars, and any other shapes without particular limitation.
The medicinal effect of the anticancer drug A of this embodiment will now be described.
The appropriate quantity for an adult to take a day is about 25-50 g. This quantity is derived from experimental results described later and equivalent to 5-10% of the daily meal quantity of an ordinary adult. The quantity may be changed appropriately depending on each person's condition. It is appropriate to divide such a daily quantity into three to five doses.
The anticancer drug A of this embodiment improves the function of the digestive organs, which increases the quantity a.
of excrement and prevents carcinogens from staying in the digestive organs. Thus, the anticancer drug A of this embodiment has a high effect in preventing cancer. Besides, the anticancer drug A of this embodiment has no side effects because its main ingredient, bamboos 1S, is natural bamboos.
Moreover, anticancer drug A prepared by using the lower no-branch culm portions of three-year-old and older bamboos as the main ingredient, bamboos IS, has a higher effect, because three-year-old and older bamboos contain more fiber, lignin, etc.
than younger bamboos do, and the lower no-branch culm portions contain more of the same than the upper branch-bearing culm 7 portions do.
Furthermore, anticancer drug A prepared from bamboos cut down during the period of three months before the season of bamboo shoots has higher effect because the bamboos contain more fiber, lignin, etc. than bamboos cut down in the other months do.
[Experiment] An experiment with the anticancer drug A of this embodiment will now be described.
10 To verify the medicinal effect of the fiber of the bamboos IS to reduce the incidence of colon and rectum cancer to be induced by dimethylhydrazine (DMH), a carcinogen, an experiment was carried out as follows.
Experimental Method 15 Male Wistar rats of about 80 g were fed with solid food on the market to acclimatize them to the feeding environment.
Then, they were divided into four groups, each consisting of The four groups were fed with different diets shown below and *observed for 20 weeks.
In the first 10 weeks, 0.03 g/kg DMH dissolved in corn oil was administered to the rats in Groups 2, 3, and 4 through a stomach tube every week. In the eleventh week, the moving speed of food through the digestive tract (from mouth to anus) and the quantity of excrement of each rat were measured. In the twentieth week, they were anesthetized with ether and their large intestines were removed. The large intestines were washed with cold physiological saline to examine them for cancer cells.
Table 2 Experimental Feed (g/kg) Group 1 Group 2 Group 3 Group 4 D M I 0 i 0 3 0 DMH 0.03 0.03 0.03 Bamboo fiber 50 100 8 Casein Corn oil Minerals Vitamins Sucrose 200 50 40 10 700 200 50 40 10 700 200 50 40 10 650 200 600 The bamboos IS were mosochiku (a species of thickstemmed bamboo or Phyllostachys pubescens). The fiber of the bamboos IS contained 56% cellulose and 24% lignin. Table 3 shows 5 the constituent parts contained in 100 g of the bamboo IS.
Table 3 Constituent Parts in 100 g of Mosochiku Constituent Parts Water Protein Lipid Sugar Fiber Ash Calcium Iron Phosphorus Tyrosine Quantity 4.98 g 1.13 g 0.22 g 48.23 g 44.39 g 1.05 g 28.00 mg 5.40 mg 34.00 mg 0.40 mg Experimental Results Table 4 shows the experimental results.
Table 4 Experimental Results Moving Speed of Food through Digestive Tract Quantity of Ex- Incidence of crement (wet Colon and weight, g/24 Rectum Cancer 9 (hours) hrs./rat) Group 1 16.9 1.5 0.6 0.2 0 (0/15) Group 2 17.2 1.2 0.6 0.3 100 (15/15) Group 3 12.5 0.9 2.5 0.3 60 (9/15) Group 4 10.2 0.6 3.2 0.4 47 (7/15) DMH was not administered to the rats of Group 1.
Accordingly, their incident of DMH-induced cancer was 0%.
DMH was administered to the rats of Group 2, but no 5 fiber of the bamboos iS was fed to them. Their incident of DMH-induced cancer was 100%.
DMH was administered and the fiber of the bamboos IS was fed to the rats of Groups 3 and 4. As the result of it, the incidences of DMH-induced cancer of Groups 3 and 4 were reduced 10 to 60% and 47%, respectively, demonstrating the effect of the fiber of the bamboos IS.
Besides, the rats of Group 4 were fed with two times the quantity of bamboo fiber fed to those of Group 3. Thus, it was demonstrated that the fiber contained in the bamboos IS reduces the incident of DMH-induced colon and rectum cancer.
^The fiber contained in the bamboos IS increased the C moving speed of food in the digestive tract and the quantity of excrement. The increased excrement can be considered to have reduced the incidence of DMH-induced colon and rectum cancer.
Namely, the fiber contained in the bamboos IS clearly reduced the incident of DMH-induced colon and rectum cancer.
As shown in Table 4, the fiber contained in the bamboos 1S increased the quantity of excrement and reduced the necessary time for food to pass through the large intestine in particular.
As the result of it, the dimethylhydrazine (DMH) was diluted to such an concentration as did not cause cancer and, at the same time, its acting time in the large intestine was reduced, which 10 resulted in the reduced incidences of DMH-induced colon and rectum cancer.
On the other hand, lignin is known to activate the immune system. The fiber of the bamboos IS contained a large quantity of lignin, which can be considered to have contributed to the reduction of incidence of colon and rectum cancer.
In these days, some people are suffering from anorexia, worrying too much about obesity with food around which tends to be rich in fat and protein. The inventor of the present invention 10 has successfully reduced his weight from 66.5 kg to 62.5 kg by having ordinary meals and taking a quantity of fiber of the bamboos IS equivalent to 5% of his daily meal quantity for days.
The inventor of the present invention has been suffering from diabetes. His blood-sugar level used to be 220-250 two hours after having a meal. It has been reduced to 160-180 by having a quantity of fiber of the bamboos IS equivalent to 5% of daily meal quantity for 60 days. In addition, his skin trouble from athlete's foot over a long time period changed from wet type to dry type and has completely been cured.
The fiber of the bamboos 1S demonstrated its S"effect to prevent obesity, decrease the cholesterol value in plasma, prevent colon and rectum cancer, and also help the treatment of skin troubles.

Claims (9)

1. A pharmaceutical composition suitable for use as an anticancer drug and comprising bamboo powder derived from a lower no branch culm portion of a three-year-old or older bamboo.
2. A pharmaceutical composition according to claim 1, wherein the bamboo powder is produced by the following process: providing, as a starting material, a lower no branch culm portion of a three-year-old or older bamboo; and grinding the starting material to a powder.
3. The pharmaceutical composition of claim 1 or 2, wherein the bamboo provided as the starting material is cut down during a period three months before the season of bamboo shoots.
4. The composition of any one of claims 1 to 3 further comprising pumpkin seed powder, wheat flour, garlic powder, powdered cheese and water.
A method of producing a pharmaceutical composition suitable for use as an anticancer drug, the method comprising: providing as a starting material a lower no branch culm portion of a three-year-old or older bamboo; and e*ee grinding the starting material to a powder.
6. A method according to claim 5 wherein the lower no branch culm portion of the three-year-old or older bamboo is cut down during a period three months before 20 the season of bamboo shoots. o..ee oooee eeoeS *S.S oeeo
21329-00.DOC 12-
7. A method according to claim 6 further comprising, after said grinding step, combining the bamboo powder with pumpkin seed powder, wheat flour, garlic powder, powdered cheese and water and allowing the mixture to mature.
8. A method for reducing the incidence of colon or rectal cancer in a subject, the method comprising orally administering to the subject a pharmaceutical composition according to any one of claims 1 to 4.
9. A method of treating cancer including the step of administering to a patient in need thereof a composition according to any one of claims 1 to 4. A method according to claim 9 wherein the cancer is cancer of the digestive tract. 11. A method according to claim 10 wherein the cancer is selected from stomach cancer, colon cancer and rectum cancer. 12. The use of a composition according to any one of claims 1 to 4 for the manufacture of a medicament for the treatment of cancer. 13. The use of a composition according to claim 12 wherein the cancer is cancer of the 15 digestive tract. 14. The use of a composition according to claim 13 wherein the cancer is selected from stomach cancer, colon cancer and rectum cancer. 15. A pharmaceutical composition according to claim 1 and suitable for use as an anticancer drug substantially as herein described with reference to the embodiment 20 of the invention given by way of example in Table 1. 16. A method of producing a pharmaceutical composition according to claim 5 and substantially as herein described with reference to any one of the embodiments of *the invention given by way of example in Figure 1. 21329-00.DOC 13 17. A method of treating cancer according to claim 9 and substantially as herein described with reference to any one of the embodiments of the invention given by way of example in the section headed Experiment. 18. The use of composition for the manufacture of a medicament for the treatment of cancer according to claim 12 and substantially as herein described with reference to any one of the embodiments of the invention given by way of example in the section headed Experiment. 19. A dietary supplement substantially as herein described with reference to any one of the embodiments of the invention given by way of example in Table 1. DATED this 16th Day of November 2000 ASAHI CORPORATION Attorney: CHARLES W. TANSEY Registered Patent Attorney of The Institute of Patent and Trade Mark Attorneys of Australia of BALDWIN SHELSTON WATERS **o **o **o 21329-00.DOC
AU87021/98A 1997-11-12 1998-09-23 Anticancer drug Ceased AU728928B2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JPH9-326981 1997-11-12
JP32698197A JP3497362B2 (en) 1997-11-12 1997-11-12 Anticancer drugs

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AU8702198A AU8702198A (en) 1999-08-26
AU728928B2 true AU728928B2 (en) 2001-01-18

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US (1) US6391307B1 (en)
EP (1) EP0919240B1 (en)
JP (1) JP3497362B2 (en)
KR (1) KR100301784B1 (en)
CN (1) CN1092977C (en)
AU (1) AU728928B2 (en)
CA (1) CA2249418C (en)
DE (1) DE69809375T2 (en)
ES (1) ES2187897T3 (en)

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AU2002217832A1 (en) * 2000-11-15 2002-05-27 Rutgers, The State University Of New Jersey Black tea extract for prevention of disease
KR100670840B1 (en) * 2004-08-20 2007-01-18 담양군 Use of Bamboo Concentrate for Enhancing Bioavailability of Taxane Family Drug
ITBA20080008A1 (en) * 2008-02-22 2009-08-23 Michele Barone COMPOSITIONS INCLUDING SELECTIVE PHYTO-EXTERGENS FOR THE ESTROGENIC BETA AND DIETARY FIBER RECEPTOR
US8125049B2 (en) * 2009-11-16 2012-02-28 International Business Machines Corporation MIM capacitor structure in FEOL and related method
US20110142993A1 (en) * 2009-12-10 2011-06-16 Timothy Bowser Method for Making Pet and Animal Comestibles

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Publication number Priority date Publication date Assignee Title
JPS62148425A (en) 1985-12-20 1987-07-02 Mitsutoyo:Kk Production of drug efficacious substance from leaf and stalk of bamboo grass
HU196559B (en) * 1987-04-17 1988-12-28 Biogal Gyogyszergyar Process for production of capsules of big stability from mild gelatine for medical purpuses containing as active substance of oils of natural origin
NO882653D0 (en) * 1988-06-15 1988-06-15 Apothekernes Lab DOSAGE FORM.
CH675685A5 (en) * 1988-06-24 1990-10-31 Flachsmann Ag Emil
EP0552478B1 (en) * 1991-12-23 1996-05-01 National Starch and Chemical Investment Holding Corporation Dietary fiber derived from tapioca

Non-Patent Citations (3)

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Title
BIOL. ABST. VOL.73 (8), 1982, ABST. NO.55480 *
J.AVD. ZOOL., VOL 10 (2), 1989, PPS 119-125, XP002094079 *
PAT. ABST. OF JAPAN VOL.011 (379) (C463), 10 DEC. 1987 *

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EP0919240B1 (en) 2002-11-13
CN1092977C (en) 2002-10-23
AU8702198A (en) 1999-08-26
CA2249418A1 (en) 1999-05-12
CA2249418C (en) 2002-07-16
JP3497362B2 (en) 2004-02-16
CN1217209A (en) 1999-05-26
KR19990044830A (en) 1999-06-25
DE69809375D1 (en) 2002-12-19
EP0919240A1 (en) 1999-06-02
KR100301784B1 (en) 2001-09-06
US6391307B1 (en) 2002-05-21
JPH11139982A (en) 1999-05-25
ES2187897T3 (en) 2003-06-16
DE69809375T2 (en) 2003-08-21

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